Prevalence and burden of vitiligo in Africa, the Middle East and Latin America

Abstract Vitiligo is a common chronic autoimmune disorder characterized by skin and hair depigmentation that affects 0.5%–2.0% of the global population. Vitiligo is associated with diminished quality of life (QoL) and psychosocial burden. The burden of vitiligo may vary based on skin tone and cultural differences as well as geographical variations in disease awareness, societal stigma, healthcare systems and treatment options. Data on the burden and management of vitiligo in Africa, the Middle East and Latin America are scarce. Literature searches using terms covering vitiligo in Africa, the Middle East and Latin America were conducted using PubMed to identify relevant publications that focused on disease prevalence and burden, QoL and psychosocial impact and disease management between 2011 and 2021. Most of the reviewed studies were conducted in the Middle East, and most Latin American studies were from Brazil. Most studies involved small patient numbers and may not be generalizable. Reported prevalence of vitiligo ranged from 0.18% to 5.3% in Africa and the Middle East, and from 0.04% to 0.57% in Latin America. In several studies, prevalence was higher among female participants. Generally, non‐segmental vitiligo was the dominant clinical variant identified and the age at onset varied widely across studies. Common comorbidities include autoimmune diseases such as Hashimoto's thyroiditis, alopecia areata and diabetes. Few treatment guidelines exist in these regions, with the exceptions of guidelines published by the Brazilian and Argentinian Societies of Dermatology. There is a clear unmet need for large epidemiological studies with uniform methodology to accurately ascertain the true prevalence of vitiligo in Africa, the Middle East and Latin America. Additional data on vitiligo burden and management in Africa and Latin America are also needed, along with local disease management guidelines that consider genetic variation, psychosocial burden and socioeconomic diversity in all 3 regions.

mucosal, localized, universal and mixed pattern).Rare subtypes are included in an undetermined/unclassified group.Segmental and non-segmental forms of the disease were originally believed to have distinct underlying pathogenetic mechanisms due to their differing clinical presentations, with somatic mosaicism being favoured for the segmental form. 3However, recent evidence suggests an overlapping inflammatory pathogenesis for both forms of the disease. 1 Global prevalence estimates for vitiligo generally range between 0.2% and 2.0%, with some geographic variation. 4,5The disease impacts children, adolescents and adults of both sexes and imparts a significant quality of life (QoL) and psychosocial burden. 1,6Vitiligo is more noticeable in individuals with darker skin tones and stigma may be influenced by cultural differences.Additionally, patients may face barriers due to disease awareness, stigma, healthcare systems and limited treatment options specific to their geographic region. 7or example, individuals with vitiligo in Brazil are disqualified from certain public professions. 8Studies that have reported higher Dermatology Life Quality Index (DLQI) scores in patients with vitiligo in the Middle East compared with those in European countries have suggested that skin colour, cultural stigma and disease education as possible factors to explain the variation. 9verall, data on the burden and management of vitiligo in Africa, the Middle East and Latin America are limited.
In this review, we aim to provide an overview of the burden of vitiligo in Africa, the Middle East and Latin America, including disease prevalence estimates, patient characteristics, genetic components and biomarkers.We review the impacts of vitiligo on patient QoL, including psychosocial impact and comorbidities.Finally, we discuss approaches to disease management and guidelines used in these regions, review the patient perspective and highlight unmet needs in current treatment paradigms.

| METHODS
For the purpose of this narrative review, PubMed searches were performed to identify relevant publications from 1 January 2011, through 22 November 2021.For retrieval of publications relating to the Africa and Middle East (AfME) regions, the search terms 'Vitiligo' AND 'Africa' OR 'Middle East' were used with additional separate searches for vitiligo and the individual countries shown in Supplementary Table S1.For retrieval of publications relating to Latin America, the search terms 'Vitiligo' AND 'Latin America' OR 'LatAm' OR 'South America' OR 'Central America' were used, with additional separate searches conducted for vitiligo and the individual countries shown in Supplementary Table S1.Titles and abstracts of the identified publications were reviewed manually, and the relevant publications were selected for inclusion in this review.

| Prevalence estimates
0,23 Relatively few studies evaluated the prevalence of vitiligo in Latin America, with estimates of 0.04%-0.57%reported in studies in Brazil and Mexico (Table 2). 4,29,32Studies included relatively few patients and there were substantial differences in the characteristics of the included populations (e.g., age, setting), limiting cross-study comparisons of vitiligo prevalence across Africa, the Middle East and Latin America.

| Patient characteristics
Selected patient demographic and disease characteristics from studies in Africa, the Middle East and Latin America are summarized in Tables 1 and 2. In AfME, most studies reported a female predominance. 18,22,25A female predominance or similar prevalence between sexes was also observed in 2 studies in Latin America. 28,32at's already known about this topic?� Vitiligo is a complex autoimmune disease with proven impact on the quality of life and psychosocial well-being of patients.� Data on the prevalence, burden and management of vitiligo in Africa, the Middle East and Latin America are scarce.

What does this study add?
� This review presents available data on the burden of vitiligo in Africa, the Middle East and Latin America, summarizes treatment guidelines and highlights unmet needs.� Prevalence of vitiligo in Africa and the Middle East ranged from 0.18% to 5.30% and from 0.04% to 0.57% in Latin America.� With the exception of guidelines from the Brazilian and Argentinian Societies of Dermatology, few treatment guidelines exist in these regions.
T A B L E 1 Epidemiological and clinical aspects of vitiligo: data from Africa and the Middle East.In terms of clinical presentation, non-segmental vitiligo (also called 'generalized vitiligo,' which was used in some studies) was generally the most common clinical variant in Middle Eastern and African patients 10,14,16,18,22,24 (e.g., 42.2% of patients with vitiligo at a Saudi Arabian dermatology clinic in a large crosssectional study 18 ).However, differences in nomenclature/classification across studies (e.g., grouping of different non-segmental variants or not) makes it difficult to compare the relative frequency of different subtypes -7 of 18 by region. 2 The sun-exposed areas of the head and neck region were the most frequently involved sites in most studies. 14,18,22,24,28he age of onset of vitiligo is not consistent, with disease occurring across age groups from children through older adults (Tables 1 and 2).Higher prevalence peaks were reported in patients in their second, third and fourth decades in studies across Africa (Benin 10 and Tanzania 22 ), the Middle East (Turkey 27 and Saudi Arabia 18 ) and Latin America (Brazil 28,34 ).Higher prevalence in older individuals was reported in a large population survey in Brazil. 29itiligo is among the most common non-infectious dermatoses in children and adolescents, 11,17,19,35 and several studies aimed to characterize childhood vitiligo in countries including Jordan, 14 Egypt 36 and Brazil. 30,31ost paediatric vitiligo cases in these regions occurred in school-aged children (i.e., 5-10 years of age 14,30 ) with a mean disease onset approximately age 6 years. 31,36Two studies in Brazil reported a predominance in girls, 30,31 with later disease onset observed in boys. 30However, one study suggested this could be due to selection bias with parents being more likely to report cosmetic-affecting conditions in girls. 31Differences in clinical features (e.g., disease activity, sites affected, clinical form) were reported in childhood versus adult-onset vitiligo. 31,36,37For example, some studies found the face, head and neck to be the most common site of onset in children and adolescents, but arms and forearms were the most common in adults 31,36 ; other studies found the prevalence of halo nevi to be higher among children and of leukotrichia to be higher in patients with adult-onset disease. 37Most childhood cases are non-segmental vitiligo (e.g., >90% in one study from Jordan). 14,36However, the segmental subtype is more common among children than adults and has an earlier age of onset. 28,30,34,36n Brazil, an association between the prevalence of vitiligo and race/latitude was reported in a large population survey, with higher prevalence observed at lower latitude and in people of non-European and Amerindian races. 29Given the scarcity of data on patterns and prevalence of vitiligo in Latin America, this study highlights the need for further studies.

| Genetic components and biomarkers
Familial cases of vitiligo are common, and a study in Brazil 34 supported an association with family history; however, relatively few Tanzanian 22 and just over 40% of Saudi Arabian 18 patients had a positive family history (Tables 1 and 2).Several studies, particularly in the Middle East, aimed to evaluate genetic components and biomarkers.However, most studies were fairly small (40 to 200 patients) pilot studies.The tumour necrosis factor (TNF) pathway has been of particular interest, with genetic mutations reported as risk factors for vitiligo in Egyptian 38 and Saudi Arabian patients. 39,40In addition, elevated serum TNFα levels have been associated with vitiligo in Iraqi 41 and Iranian patients. 40[44][45][46][47][48][49][50] 3.4 | Comorbidities, psychosocial effects and QoL

| Impact of vitiligo on QoL
6][57][58] Multiple DLQI translations are available, including Arabic and Portuguese versions. 9,54,59An Egyptian Arabic version of the Skindex-16 60 is also available.To account for social, religious and cultural aspects unique to some regions, a new patient questionnaire was self-developed to evaluate the QoL of patients with vitiligo in Saudi Arabia. 61Given the clinical characteristics of vitiligo (e.g., lack of physical symptoms/pain), use of a disease-specific instrument like the VitiQoL is more informative than a more general instrument like the DLQI or Skindex-16.
Despite availability of multiple adaptations of commonly used QoL scales for use in these regions, data on QoL remain limited.Recent studies in patients from AfME and Latin America are summarized in Tables 3 and  4, respectively.Most included small numbers of patients, and variations in designs/instruments limit generalizability and cross-study comparisons.Among Brazilian patients, vitiligo was among the skin diseases that most impacted QoL, second to psoriasis. 54Moderate QoL impairments were also reported in Tanzanian patients (using the DLQI instrument). 21However, small-to-no impairments were observed in Saudi Arabian 59 (using the DLQI instrument) and Mexican 33 patients (using both the DLQI and VitiQoL instruments).
DLQI and VitiQoL items related to stigmatization were impacted among Nigerian 51 and Brazilian 53 patients.Several studies note greater QoL impairment in women versus men 53,58,61 and in patients with genital lesions. 33Patients with comorbid psychiatric disease may be particularly vulnerable to the adverse QoL impact of vitiligo. 53

| Psychosocial impact
A recent global systematic review of psychosocial burden in patients with vitiligo highlighted the prevalence  of a variety of psychosocial comorbidities, including high prevalence (>50%) of depression, major depressive disorder, sleep disturbances, avoidance and restriction behaviour, self-consciousness, emotional impairment, relationship difficulties and cognitive impairment. 6However, very few studies have evaluated psychosocial burden in Africa and Latin America. 6,33ecent studies evaluating psychosocial impact in patients with vitiligo from Africa, the Middle East and Latin America are summarized in Table 5.These studies highlight the need to evaluate psychosocial comorbidities among patients with vitiligo to form a complete clinical picture and identify patients that may benefit from psychological interventions. 63

| Other comorbidities
8][69] In particular, high rates of autoimmune thyroid disease were reported in adult and paediatric patients in Brazil, Iran, Saudi Arabia and Turkey 18,26,[67][68][69] ; however, another Turkish study reported relatively low rates of impaired thyroid function and thyroid autoantibodies. 70o-occurrence with other dermatologic conditions has been demonstrated. 18,26,71,72For example, vitiligo was reported in 1%-5% of Tunisian patients with alopecia areata (AA). 71Conversely, AA was reported in 5% of Turkish patients with vitiligo. 26A high degree of co-occurrence between vitiligo and psoriasis was observed among Iranian patients. 72omorbidities reported in patients with vitiligo include diabetes, dyslipidaemia, obesity and hypothyroidism (Saudi Arabia) and hypertension (Iran 73 and Turkey 26 ).
Conclusions regarding associations between vitiligo and comorbid autoimmune, dermatological and other conditions are limited by small sample sizes in most studies, lack of consistent design/assessments across studies, and inability to attribute causality; there is a need for further studies particularly in Latin America.

| Disease management and treatment guidelines
The goal of vitiligo treatment is to halt the progression of the disease, and stimulate and maintain repigmentation thus avoiding psychosocial disease sequalae. 74Combination therapies have proven to be more effective than monotherapy 75 and include phototherapy with narrow-band ultraviolet B (NB-UVB) -either local or full body-together with topical calcineurin inhibitors.Alternative combination therapy consists of excimer laser plus topical calcineurin inhibitors.The recent US Food and Drug Administration (FDA) approval of topical ruxolitinib 1.5% cream for non-segmental vitiligo in patients aged ≥12 years 76 highlights a new era in vitiligo treatment as it is the first FDA-approved topical medication for vitiligo.
Our literature review highlighted that disease management approaches typically involve topical or systemic immunosuppressants, phototherapy and/or surgical techniques. 1 In a survey among Saudi Arabian dermatologists, most (76%) did not view vitiligo as a purely cosmetic problem and 69% encouraged treatment, most commonly with topical corticosteroids (TCS) and NB-UVB phototherapy. 77ublished regional and country-specific treatment guidelines are generally lacking in Africa, the Middle East and Latin America; there remains a need for national evidence-based guidelines reflecting unique patient features in the different regions to standardize care and improve patient outcomes. 7One notable exception is the 2020 guidelines on the treatment of vitiligo by the Brazilian Society of Dermatology, which provide a consensus on clinical and surgical treatment based on best scientific evidence available to date (Supplementary Table S2). 74Guidelines from the Argentinian Society of Dermatology are also available (Supplementary Table S2). 78Brazilian, Argentinian and international guidelines define standard treatment as TCS and calcineurin inhibitors for unstable and localized cases and corticosteroid oral mini-pulse therapy for unstable generalized cases. 1,79In the few regional studies that included information about treatment, TCS were commonly used in Brazilian and Tanzanian patients. 22,30Brazilian guidelines, published prior to the FDA approval of ruxolitinib in 2022, also highlighted that topical and systemic anti-Janus kinase agents and anti-interleukin 15 receptor immunobiologicals are in development. 74onsistent with frequent use of phototherapy, vitiligo was the most common diagnosis underlying referral to phototherapy among Brazilian dermatology patients. 80Phototherapy included NB-UVB, excimer laser, excimer lamp and psoralen (oral and topical) ultraviolet A (PUVA). 1,74Brazilian guidelines recommend NB-UVB phototherapy as the treatment of choice for repigmentation, noting that excimer laser techniques are not appropriate for patients with extensive affected areas and are associated with higher costs. 74Argentinian guidelines recommend the use of NB-UVB phototherapy as first-line treatment (Supplementary Table S2) and provide direction on the use of excimer light/laser treatment. 78Consistent with typical practice in other regions such as Europe, 1 surveyed Saudi Arabian dermatologists typically chose NB-UVB for T A B L E 5 Psychosocial impact of vitiligo: data from Africa, the Middle East and Latin America.generalized vitiligo, while excimer laser was most commonly used to treat focal and segmental vitiligo. 81n a clinical trial in Saudi Arabia (N = 48), 308-nm excimer laser treatment was effective and improved psychosocial QoL, particularly among female patients. 82razilian guidelines recommend that surgical modalities be reserved primarily for stable segmental disease and generalized vitiligo, with phototherapy before and after surgical treatment. 74Pilot studies involving suction blister epidermal graft and non-cultured epidermal cell suspension for surgical vitiligo management were recently conducted in Brazil. 79,83][86][87] Tailored personalized treatment is required for optimal treatment of vitiligo, and some patients prefer cosmetic camouflage or depigmentation approaches. 1 However, Brazilian guidelines recommend against several commonly used depigmentation approaches. 74eal-world limitations to achieving appropriate treatment include the availability of phototherapy across centres and insurance coverage only funding a limited number of sessions.

| Disease education and awareness
In a 2015 survey of Turkish patients with vitiligo, most had knowledge about their illness and its causes. 25owever, public misconceptions and attitudes about vitiligo were identified in Saudi Arabian surveys. 18,88isconceptions included vitiligo being of infectious origin and due to lack of hygiene.Few patients (4.3%; N = 4134) recognized that loss of pigment cells was a cause of vitiligo. 18 survey of Iranian dermatologists indicated that most (66%) were interested in continuing medical education regarding psychodermatology, highlighting the need for collaboration between dermatologists and psychiatrists to improve QoL in patients with dermatological conditions. 89

| The patient's journey
There is substantial variability in the time to seek consultation, with variable disease at presentation within and between studies in these regions (Tables 1  and 2).In most parts of the world, the family physician or paediatrician is the first contact for patients with vitiligo, due to their easy accessibility.Depending on these physicians' experience in managing vitiligo, patients may receive initial treatment or be referred to a dermatologist causing a lag in receiving specialist care due to delays in diagnosis and treatment due to wait times or lack of access to specialist care. 7There are currently no data available from Africa, the Middle East nor Latin America pertaining to first contact with physicians accessed by patients with vitiligo.
Low treatment adherence has been reported among Egyptian and Saudi Arabian patients 90,91 and may present a barrier to disease management.Higher adherence is associated with oral treatment/phototherapy, while adherence is particularly low among patients who view treatment as stigmatizing 90 and those worried about side effects. 91Public misconceptions about vitiligo (e.g., infectious origin) identified in a Saudi Arabian survey 88 may also impact seeking treatment.

| Unmet needs
Current data on the epidemiology, QoL/psychosocial impact and management of vitiligo in Latin America are scarce.Most studies come from Brazil and may not be representative of the region as a whole.As such, there is a significant need for local epidemiological studies in different populations.There is also a need for current local disease management guidelines that consider the genetically and socioeconomically diverse patient populations in the different regions.
There is often a long duration of vitiligo before patient presentation at a dermatology clinic. 7The recent FDA approval of ruxolitinib cream in adolescents and adults heralds a new era in vitiligo treatment.With many new similar topical and systemic drugs in the pipeline, the future of vitiligo treatment appears to be bright, and dermatologists in the region will soon be better equipped with an armamentarium of treatment options to offer their patients with vitiligo.However, not all patients may have access to treatments due to resource limitations in some regions. 7hile a number of medical, phototherapy and surgical approaches are under evaluation in clinical trials, there is a need for standardized disease nomenclature and outcomes.It will be important to agree on a set of 'core outcomes' to be assessed and reported across clinical trials.One study aimed to develop international consensus on a core outcome set for vitiligo trials and determined that repigmentation, side effects and maintenance of gained repigmentation should be measured in all future trials. 92Furthermore, new instruments are being developed to reliably measure disease outcomes.For example, the Vitiligo Extent Score was developed as a physician global assessment for disease extent, with defined categories for extent. 93

| Future prospects in minimizing the burden of vitiligo in Africa, the Middle East and Latin America
As much as possible, dermatologists need to work interdisciplinarily with psychologists or psychiatrists to address the individual problems of each patient.Education of the primary care physician regarding the need for early referral of patients with vitiligo to dermatologists will also be important.In resource-poor settings such as Africa, the Middle East and Latin America, the primary care physician may be the sole physician in contact with patients.Hence, continuous education regarding basic knowledge and updates in vitiligo management should be periodically imparted to healthcare providers, specifically given the stigma associated with the disease.
There is also a need for patient education programmes and patient support groups to combat the myths and stigmas associated with vitiligo and to encourage patients to visit a dermatologist early in the course of their disease.Public awareness campaigns and education may help revert misconceptions, myths and negative attitudes towards vitiligo.

| LIMITATIONS
This narrative review included a wide literature search to cover multiple aspects of the burden of vitiligo in Africa, the Middle East and Latin America; however, relevant articles may potentially have been excluded because of the chosen search terms.In addition, the absence of systematic review methodology may have resulted in possible bias in the articles chosen.

| CONCLUSIONS
There is a substantial burden of vitiligo in Africa, the Middle East and Latin America, in terms of disease prevalence, QoL and psychosocial impact on patients and their families.Most of the studies reviewed were conducted in the Middle East, and the majority of studies in Latin America were from Brazil.There is an unmet need for large epidemiological studies with uniform methodology to accurately ascertain the true prevalence of vitiligo in Africa, the Middle East and Latin America.There is also a need for additional data on vitiligo burden and management in African and Latin American populations.
Epidemiological and clinical aspects of vitiligo: data from Latin America.
T A B L E 2AL HAMMADI ET AL.

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Mean VitiQoL: 30.51 � Quality of life in patients with vitiligo: Data from Latin America.
Abbreviations: DLQI, Dermatology Life Quality Index; FDLQI, Family Dermatology Life Quality Index; QoL, quality of life; SS, Stress Score; VitiQoL, Vitiligo-Specific Health-Related Quality of Life instrument.aFor the overall population of 500 patients with a dermatologic diagnosis; demographic data for the subset of patients with vitiligo not reported.bForthe overall population of 391 patients attending a dermatology outpatient clinic; demographic data for the subset of patients with vitiligo not reported.10 of 18 -AL HAMMADI ET AL.T A B L E 4 • Mean age: 38 years • Mean (SD) VitiQoL score was 32.1 (22.7) of maximum score of 90 Abbreviations: CDLQI, Childhood Dermatology Life Quality Index; DLQI, Dermatology Life Quality Index; QoL, quality of life; VitiQoL, Vitiligo-Specific Health-Related Quality of Life instrument.aFor the overall population of 548 patients attending a dermatology outpatient department; demographic data for the subset of patients with vitiligo not reported.AL HAMMADI ET AL.